Systemic hypoxia promotes lymphocyte apoptosis induced by oxidative stress during moderate exercise

Blood undergoes oxidative stress during severe hypoxia or intense exercise. Excessive exposure to oxidative stress induces replicative senescence and apoptosis of lymphocytes. This study determines how various exercises with/without hypoxia affect lymphocyte subset mobilization and oxidative stress-induced lymphocyte apoptosis. Eighteen sedentary males randomly engaged in two normoxic exercise bouts [severe exercise (SE) (up to VO(2max)) and moderate-intensity exercise (ME) (50%VO(2max)) while exposed to 21%O(2)], two hypoxic exercise bouts (ME while exposed to 12%O(2) and 15%O(2)) and two hypoxic resting conditions (resting while exposed to 12%O(2) and 15%O(2)) in a normobaric hypoxia chamber. Under normoxic conditions, SE but not ME (1) increased the percentages of senescent (CD28(-) and CD57(+))/activated (CD62L(-) and CD11a(+))-form lymphocytes mobilized into the peripheral blood compartment; (2) decreased the levels of surface thiol and intracellular total (t-GSH) and reduced-form glutathione (r-GSH) of lymphocytes in blood; and (3) further enhanced the extents of H(2)O(2)-induced mitochondria trans-membrane potential diminishing, caspases 3/8/9 activation, poly(ADP-ribose) polymerase cleavage and phosphotidyl serine exposure in blood lymphocytes. However, no significant change occurred in the subset mobilization, antioxidant levels or apoptosis of lymphocytes following exposure to either 12%O(2) or 15%O(2). Although both 12%O(2) and 15%O(2) ME increased the mobilization of senescent/activated-form lymphocytes, only 12%O(2) ME enhanced H(2)O(2)-induced lymphocyte thiol, t-GSH and r-GSH consumption and apoptotic responses. Therefore, we conclude that the 12%O(2) exposure increases the mobilization of senescent/activated-form lymphocytes into the peripheral blood compartment and simultaneously enhances oxidative stress-induced lymphocyte apoptosis by diminishing cellular antioxidant levels during exercise.